Solitary neuroendocrine-like (small granule) cells were examined for their distribution in the upper airways of the guinea pig and for their capacity to regenerate in xenografts maintained subcutaneously in the nude mouse. The solitary cells were present in the larynx at a frequency of about 5% in guinea pigs of various ages: less than 1% of the glandular epithelial cells were of the neuroendocrine-type. In the trachea the frequency diminished caudally and constituted less than 1% in the bronchi. Only one population of solitary cells was observed throughout the study. The mucociliary epithelium in sections of the laryns (cricoid region) xenografted in nude mice was replaced by squamoid-like cells in one week. A normal-appearing mucociliary epithelium regenerated after one month. The full complement of small-granule cells was only attained in those regions exhibiting full maturation of the epithelium, indicating that such cells are derived from the airway epithelium as a late-stage event of cytodifferentiation.